U.S. patent application number 17/582677 was filed with the patent office on 2022-07-28 for automatic monitoring of fluid injection procedures using a sensing catheter.
The applicant listed for this patent is The Board of Trustees of the Leland Stanford Junior University. Invention is credited to Bruce L. Daniel, Lawrence V. Hofmann, Alexander Michael Vezeridis.
Application Number | 20220233770 17/582677 |
Document ID | / |
Family ID | |
Filed Date | 2022-07-28 |
United States Patent
Application |
20220233770 |
Kind Code |
A1 |
Vezeridis; Alexander Michael ;
et al. |
July 28, 2022 |
Automatic monitoring of fluid injection procedures using a sensing
catheter
Abstract
A method of monitoring a fluid injection procedure is provided.
The method includes: disposing a sensor on a catheter, where the
sensor is in proximity to a tip of the catheter; inserting at least
the tip of the catheter into a patient; delivering a fluid to a
location within the patient via the tip of the catheter; and
automatically monitoring a sensor signal from the sensor while the
fluid is being delivered. Reflux end-point detection using an
electrical impedance sensor has been demonstrated in a phantom.
Applications include embolotherapy and angiography.
Inventors: |
Vezeridis; Alexander Michael;
(Los Altos, CA) ; Daniel; Bruce L.; (Stanford,
CA) ; Hofmann; Lawrence V.; (Stanford, CA) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
The Board of Trustees of the Leland Stanford Junior
University |
Stanford |
CA |
US |
|
|
Appl. No.: |
17/582677 |
Filed: |
January 24, 2022 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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63140511 |
Jan 22, 2021 |
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International
Class: |
A61M 5/168 20060101
A61M005/168; A61M 5/00 20060101 A61M005/00 |
Goverment Interests
GOVERNMENT SPONSORSHIP
[0002] This invention was made with Government support under
contract TR003142 awarded by the National Institutes of Health. The
Government has certain rights in the invention.
Claims
1. A method of monitoring a fluid injection procedure, the method
comprising: disposing a sensor on a catheter, wherein the sensor is
in proximity to a tip of the catheter; inserting at least the tip
of the catheter into a patient; delivering a fluid to a location
within the patient via the tip of the catheter; and automatically
monitoring a sensor signal from the sensor while the fluid is being
delivered.
2. The method of claim 1, wherein the fluid injection procedure is
angiography.
3. The method of claim 1, wherein the fluid injection procedure is
embolotherapy.
4. The method of claim 1, wherein delivery of the fluid to the
patient is performed under closed loop control using the sensor
signal as an input to a control system.
5. The method of claim 1, wherein the tip of the catheter is
located within a blood vessel of the patient while the fluid is
being delivered.
6. The method of claim 5, wherein the sensor signal can be further
used to sense perforation or dissection of the blood vessel by the
catheter.
7. The method of claim 1, wherein the sensor is an electrical
impedance sensor.
8. The method of claim 7, wherein the sensor signal is at a
predetermined frequency, and wherein the predetermined frequency is
selected to provide an impedance contrast between the fluid and
blood.
9. The method of claim 7, wherein a composition of the fluid is
selected to provide an impedance contrast between the fluid and
blood.
10. The method of claim 7, wherein the sensor signal is an
impedance spectrum at a predetermined frequency range.
11. The method of claim 1, wherein the sensor is selected from the
group consisting of: optical sensors, pressure sensors, temperature
sensors, acoustic/ultrasound imaging sensors, and electrical
sensors.
12. The method of claim 1, wherein the monitoring includes
detection of a condition selected from the group consisting of:
stasis of flow of the fluid, near-stasis of flow of the fluid, free
flow of blood and reflux of the fluid.
13. The method of claim 1, further comprising performing automatic
end-point detection for the fluid injection procedure using the
sensor signal.
14. The method of claim 1, wherein the fluid injection procedure is
selected from the group consisting of: intra-arterial injection of
gene therapy, intra-arterial injection of cellular therapy,
intra-arterial injection of immune therapy, intra-arterial
injection of chemotherapy, and intra-arterial injection of
radiation therapy.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from U.S. Provisional
Patent Application 63/140,511 filed Jan. 22, 2021, which is
incorporated herein by reference.
FIELD OF THE INVENTION
[0003] This invention relates to monitoring of fluid injection
procedures performed with a catheter.
BACKGROUND
[0004] In conventional medical practice, X-rays are required for
angiography and monitoring of embolic material delivery through
angiography catheters (to block blood flow to tumors or organs). If
contrast or embolic material are injected at a rate that is too
high, the contrast or embolic material will "reflux" backward
around the catheter into anatomic regions or organs other than the
ones intended. This is a problem because it can lead to embolic
material traveling to healthy organs, and potentially damaging them
(a phenomenon known as "off target embolization"). Similarly,
reflux may occur with contrast material delivery for diagnostic
angiography, in which case it may lead to contrast material
highlighting other organs and causing diagnostic confusion,
potentially missing tumors or vascular injuries from the desired
vessels and potentially requiring repeat angiography. To avoid
these problems, angiographers watch the delivery of embolic
material using X-rays. However, X-rays are ionizing radiation that
are dangerous for the patient and the physicians performing the
procedure. Therefore, a critical problem exists that angiography
and embolization require X-rays for monitoring.
SUMMARY
[0005] To solve this problem, we have embedded an electrical
impedance sensor just proximal to the tip of the angiography
catheter. The sensor detects electrical impedance changes in
injected contrast or embolic material, allowing embolization to be
monitored without reliance on X-rays.
[0006] An exemplary embodiment has an electrical impedance sensor
just proximal to the tip of an angiography catheter. When nothing
is being injected through the catheter, the sensor is surrounded by
blood, which has a characteristic electrical impedance range. When
contrast and/or embolic material are injected at a low rate and
there is no reflux, the sensor will still be surrounded by blood
and will reflect the impedance measurement of blood. This condition
is termed forward flow of fluid, whereby blood carries the injected
fluid forward. When contrast and/or embolic material are injected
at an excessively high rate, or embolization is nearing completion,
the sensor will become surrounded by contrast material and/or
embolic material and the impedance measurement will change.
Specifically, if the impedance measurement changes to a value equal
to that of contrast material and/or embolic material, it would
indicate reflux of the injected material around the catheter. If
the impedance measurement changes to a value intermediate between
blood and the injected material and this value remains steady, this
would indicate stasis. In the field of angiography, there is a
concept of `near stasis,` which represents slowing of the blood
going to an organ but not to the degree of stasis. For some
embolization procedures, some angiographers use near stasis as an
end-point of treatment. In the context of impedance sensing
described here, near stasis could be detected as a change in the
impedance measurement to a value intermediate between blood and the
injected material which changes back to blood at a rate determined
by the residual flow of blood into the organ of interest. This rate
could provide a quantitative metric of the degree of near
stasis.
[0007] The sensor could embody a variety of 2, 3, or 4 wire
electrical impedance measurement techniques, but in present
experiments it is a two wire technique for easier fabrication. The
sensing element includes two electrodes, which in current form are
composed of conductive epoxy on top of wire leads, though
conductive swaged marker bands bonded to wire leads or wrapped wire
electrodes are an alternative. The wires run down the shaft of the
catheter to the catheter hub, where they separate into leads that
connect to the sensing circuitry. The sensing circuitry employs
transimpedance measurement techniques with or without lock-in
amplification. In current form, the circuitry sends values through
wired connection or wirelessly to a computer that is able to show
the impedance measurements as a continuous real-time graph.
[0008] For embolization, the reflux-sensing catheter promises to
decrease the amount of radiation required for embolization, and to
potentially eliminate off-target embolization. Decreased radiation
would allow safer angiography for both the patient and physician,
potentially also allowing the targeting of more lesions in a single
treatment session (which is often limited by maximum permissible
radiation to avoid negative deterministic of radiation). By
eliminating off-target embolization, the reflux sensing catheter
will preserve the health of adjacent organs.
[0009] For diagnostic angiography, the reflux-sensing catheter
promises to avoid excessive contrast agent injection which create
poor or nondiagnostic angiographic pictures. A common scenario is
that a catheter ejects out of the target vessel due to excessive
injection force. We envision a closed-loop control system enabled
by a sensing catheter, whereby if reflux is sensed, the injection
rate is automatically decreased. Currently, when this situation
occurs, the injection is not stopped and the patient receives the
full contrast agent load. As contrast agents can be damaging to the
kidneys, it is desirable to avoid such a situation.
[0010] Also for both diagnostic angiography and embolization, we
envision that the sensing element could be used to indicate that
the catheter has perforated and/or dissected the blood vessel it is
located in.
[0011] Advantages include: [0012] decreased radiation required
during angiography and embolization procedures, leading to enhanced
safety for patient and physician; [0013] safer embolization
procedures with less risk of off-target embolization; [0014]
potential ability to target more tumors/organs if less radiation is
required for each tumor/organ.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIGS. 1A-B show an example of conventional X-ray monitoring
of embolization therapy.
[0016] FIGS. 2A-C schematically show operation of an exemplary
monitoring method according to an embodiment of the invention.
[0017] FIGS. 3A-C schematically show monitoring data obtained from
an embolization phantom.
[0018] FIG. 4 shows electrical impedance vs. frequency for several
relevant fluids.
DETAILED DESCRIPTION
[0019] Embolization through angiography catheters has been a
revolutionary targeted treatment, providing a minimally-invasive
substitute for morbid surgical procedures and enabling therapies
previously not possible. As part of the embolization process, small
particles and fluids are delivered to organs through angiography
catheters, with the intention of stopping bleeding in trauma,
blocking blood flow to tumors, delivering chemotherapy to tumors,
or decreasing blood flow to benign yet debilitating conditions like
uterine fibroids or enlarged prostates. The applications of
embolization are widespread, with indications continuing to
expand.
[0020] However, transcatheter embolization has a critical weakness:
it requires X-ray imaging to assess the progress and end-points of
embolization. X-rays are ionizing radiation, subjecting patients
and treating physicians to DNA damage and the consequent dangers of
radiation (skin injury, cataracts, cancer). Physicians performing
embolization therefore must wear heavy protective equipment, which
lead to high rates of occupational injury. Alarmingly, despite
protection and radiation dosimetry, recent studies are showing that
interventionalists have higher rates of chromosomal damage. Aside
from the concerns of radiation safety, most embolic material cannot
be directly visualized on X-ray. Thus, embolic material is
typically suspended in iodinated contrast media so its delivery can
be monitored with X-ray, but visualization remains challenging,
especially in larger patients. X-rays are therefore an indirect and
imperfect means of monitoring embolic delivery and off-target
embolization. Moreover, patients with kidney failure or prior
contrast-reaction cannot receive iodinated contrast media. FIGS.
1A-B show an example of conventional X-ray monitoring of
embolization therapy. FIG. 1A is an X-ray image showing no reflux
near catheter tip 102. FIG. 1B is an X-ray image showing reflux 104
around the catheter tip. As is apparent from these images, it can
be challenging to accurately monitor the procedure.
[0021] To solve the reliance of embolization monitoring on
dangerous X-rays, we integrate electrical impedance sensors at the
tip of the angiography catheter that can sense the progress of
embolization without the need for X-rays. The implementation of the
aforementioned sensing angiographic catheter prototype involved
attaching fine wire leads to the catheter with silver epoxy, which
would be too fragile and too bulky for clinical use. Therefore,
subsequent prototypes were created using thin-film metal electrodes
via micro/nanofabrication techniques and are preferred due to their
low profile, facilitating navigation through blood vessels.
[0022] Preliminary data confirms that electrical impedance sensing
at the catheter tip is a feasible approach to replacing X-ray
monitoring of embolization. First, the electrical impedance spectra
of several fluids regularly encountered during embolization were
measured (FIG. 4). Blood exhibited an impedance spectrum very
different from the carrier media often used for embolic delivery
(nonionic iodine contrast or dextrose solution), meaning that when
the carrier medium becomes static as the target organ fills with
embolic, the carrier medium will displace blood and the sensor will
register a different impedance value (FIGS. 2A-C).
[0023] Here FIG. 2A shows delivery of embolization material to
blood vessels 204 feeding a mass 202 using a catheter 206. FIG. 2B
shows the undesirable reflux condition, where too much embolization
material is provided and the excess gets into blood vessel 208 that
should not be embolized. FIG. 2C shows the idea of end-point
detection, where a sensor 210 is used to determine when the
embolization material reaches the sensor in order to provide a
suitable signal for ending the therapy.
[0024] Accordingly, an embodiment of the invention is a method of
monitoring a fluid injection procedure, where the method includes:
disposing a sensor on a catheter, where the sensor is in proximity
to a tip of the catheter; inserting at least the tip of the
catheter into a patient; delivering a fluid to a location within
the patient via the tip of the catheter; and automatically
monitoring a sensor signal from the sensor while the fluid is being
delivered.
[0025] Delivery of the fluid to the patient can be performed under
closed loop control using the sensor signal as an input to a
control system.
[0026] The tip of the catheter can be located within a blood vessel
of the patient while the fluid is being delivered.
[0027] In such cases, the sensor signal can be further used to
sense perforation or dissection of the blood vessel by the
catheter.
[0028] In phantom experiments, a 5 French (1.67 mm diameter)
angiographic catheter was fitted with two electrodes near its tip
to perform two-wire electrical impedance measurements in a flow
phantom model (FIGS. 3A-C). Here 302 is the flow phantom, 304 is
the modeled embolic carrier medium, 306 is the impedance sensor on
the catheter, 308 is an impedance threshold separating forward flow
from stasis or near-stasis, and 310 is an impedance threshold
separating stasis from reflux.
[0029] Since saline has an electrical impedance value similar to
blood, red colored normal saline was used as a blood mimicking
fluid. Blue-colored 5% dextrose solution in water (a possible
carrier medium for embolic material) was then injected through the
angiography catheter into a target vessel of the phantom. As the
vessel filled with the embolic carrier medium (dextrose solution)
and started to reflux around the catheter tip and impedance
sensor--which in the setting of embolization would indicate that
delivery should be slowed--the electrical impedance value changed
from that of the blood mimicking fluid to that of the embolic
carrier medium (progression from FIG. 3A to FIG. 3C).
[0030] FIG. 4 shows electrical impedance vs. frequency for several
relevant fluids.
[0031] Practice of the invention is not limited to end-point
detection. These principles are applicable to any kind of automated
monitoring of a fluid injection procedure, such as: detecting
stasis of flow of the fluid, detecting near-stasis of flow of the
fluid, detecting free flow of blood and detecting reflux of the
fluid. Details of how these flow regimes are best defined will
depend on specifics of the therapy being performed, but can be
determined in each case by straightforward experimentation.
[0032] Practice of the invention is also not limited to electrical
impedance sensing on the catheter. Suitable catheter sensors could
be optical sensors, pressure sensors, temperature sensors,
acoustic/ultrasound imaging sensors, and/or electrical sensors.
Naturally, it is preferred for the sensor technology to be
compatible with the catheter being used.
[0033] In cases where the sensor is an electrical impedance sensor
the sensor signal can be at a predetermined frequency that is
selected to provide an impedance contrast between the fluid and
blood. Alternatively or in addition, the composition of the fluid
can be selected to provide an impedance contrast between the fluid
and blood. The sensor signal can also be an impedance spectrum at a
predetermined frequency range. Such a multi-frequency signal can
provide `fingerprints` to more clearly distinguish the fluid being
injected from blood. More generally, any sensor technology that can
provide a multi-frequency sensor signal can be used to provide such
fingerprints.
[0034] The preceding examples mainly relate to embolotherapy. There
are several versions of this. Embolotherapy can involve delivering
therapies including: liquid embolics (including cohesive embolics
such as ethylene vinyl oxide, adhesive embolics such as glue, or
sclerosants such as alcohol or sodium tetradecyl sulfate), particle
embolics suspended in liquid, or gas embolics.
[0035] Practice of the invention is not limited to embolotherapy.
It is applicable to any therapy where fluid (i.e. a liquid or a
gas) is injected into a patient's body using a catheter. An
important further application is angiography, as described above.
Carbon dioxide gas is a possible contrast agent in angiography.
[0036] Further examples of fluid injection procedures include:
intra-arterial injection of gene therapy, intra-arterial injection
of cellular therapy, intra-arterial injection of immune therapy,
intra-arterial injection of chemotherapy, and intra-arterial
injection of radiation therapy.
* * * * *